Research Interests
Tumor cell biology and drug resistance

My laboratory has been focusing on understanding of the molecular basis of tumorigenesis and tumor drug resistance.
Post-translational modifications play a pivotal role in regulating cellular functions because vast majority of critical proteins, such as transcription factors and nuclear receptors, are subject to such modifications. Small ubiquitin-related modifier (SUMO) conjugations or sumoylation has been recently identified and implicated in regulating a variety of cellular pathways. Like ubiquitination, sumoylation is a multiple step process, involving maturation, activation, conjugation and de-conjugation. As an E2 conjugating enzyme, Ubc9 is essential for sumoylation. Although it is well demonstrated that alterations of ubiquitination pathways can lead to development of cancer, the role for sumoylation in this aspect is unclear. Our recent studies have indicated that Ubc9 plays a role in tumorigenesis. Our long-term goals are to better understand the basis for Ubc9-mediated tumorigenesis and to develop Ubc9-based therapeutic agents for cancer treatment.
A second project is on microRNAs. MicroRNAs are a class of naturally occurring small non-coding RNAs that control gene expression through post-transcriptional regulation. To date, over 400 human microRNAs have been reported. Of interest, aberrant expression of microRNAs has been associated with human disorders, in particular cancer. While some microRNAs function as tumor suppressor, others function as oncogenes. We have recently shown that mir-21 is overexpressed in several types of tumors compared to the matched normal tissues and that more importantly, suppression of mir-21 by a mir-21 inhibitor substantially reduces tumor growth in a xenograft carcinoma mouse model, suggesting that mir-21 is an oncogenic microRNA. we believe that microRNAs play a critical role in cancer initiation, progression and metastasis, and thus, they, in particular oncogenic microRNAs such as mir-21, are novel therapeutic targets. Therefore, characterization of microRNA pathways leading to tumorigenesis will provide new insight into molecular mechanisms underlying microRNA-mediated gene regulation. As a result, this knowledge will aid in developing microRNA-based therapeutic agents for cancer therapy.

Selected Publications

Wu F, Stutzman A, Mo YY. 2007. Notch signaling and its role in breast cancer. Front Biosci. In press.
Pub Med

Wu F, Chiocca F, Beck WT, Mo YY. 2007. Gam1-associated alterations of drug responsiveness through activation of apoptosis. Mol Cancer Therapeutics, In press.

Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007 Mar 15; [Epub ahead of print] PMID: 17363372 [PubMed - as supplied by publisher]

Mirski SE, Sparks KE, Friedrich B, Kohler M, Mo YY, Beck WT, Cole SP.  Topoisomerase II binds importin alpha isoforms and exportin/CRM1 but does not shuttle between the nucleus and cytoplasm in proliferating cells. Exp Cell Res. 2007 Feb 1;313(3):627-37. Epub 2006 Nov 10.PMID: 17182034 [PubMed - indexed for MEDLINE]

Wu F, Mo YY.  Ubiquitin-like protein modifications in prostate and breast cancer. Front Biosci. 2007 Jan 1;12:700-11. PMID: 17127330 [PubMed]